Splenic MZL is a rare type of indolent B-cell lymphoma. Because of its low incidence, no randomized trials for splenic MZL are available and treatment options are usually evaluated based on retrospective analyses. The aim of this study was to prospectively evaluate the efficacy and safety of first-line bendamustine and rituximab (B-R) combination treatment in patients with splenic MZL. The primary endpoint was complete response rate (CRR). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), duration of response (DoR), event-free survival (EFS), overall survival (OS), and safety.

Twice a week prophylaxis with valaciclovir (500 mg, once a day) and trimethoprim/cotrimoxazole (800 mg, twice a day) was recommended for all patients during all B-R cycles

Patients achieving complete response (CR) after three cycles received only one additional B-R cycle. Those achieving partial response (PR) received three additional B-R cycles. Patients not achieving at least PR after three courses were withdrawn from the study

Results

Forty-five out of N = 56 patients completed treatment (80%):

Received four B-R cycles: n = 7 (12%)

Received six B-R cycles: n = 38 (68%)

B-R discontinuation: n = 11 (20%)

B dose reduction: n = 4

Final analysis after 3 B-R cycles (by local clinicians):

CR, n = 7: 13% (95% CI, 5–24)

PR, n = 39: 70% (95% CI, 56–81)

ORR (CR + PR): 82% (95% CI, 72–92)

Final analysis (centralized review based on the intention-to-treat principle):

CR, n = 41 (34 CR and 7 unconfirmed CR [CRu]): 73% ( 95% CI, 60–84)

PR, n = 10: 18% (95% CI, 9–30)

ORR, n = 51: 91% (95% CI, 80–97)

Stable disease (SD), n = 4: 7% (95% CI, 2–17)

Median observation time (range) = 32 months (2–52)

Three relapses observed

Three-year DoR: 93% (95% CI, 81–98)

Three-year PFS estimate: 90% (95% CI, 77–96)

Three-year EFS estimate: 80% (95% CI, 65–89)

Three-year OS estimate: 96% (95% CI, 84–98)

Safety

Any grade adverse events (AEs): n = 50 patients (89%)

Treatment-related Grade ≥ 3 AEs: n = 38 patients (68%)

Five patients discontinued treatment due to toxicity

Most common hematological Grade ≥ 3 AEs:

Neutropenia: n = 24 (42.8%)

Thrombocytopenia: n = 9 (16.1%)

Anemia: n = 5 (8.9%)

Non-hematological AEs were almost all Grade 1–2 (only three cases of Grade ≥ 3), most common:

Nausea/vomiting (Grade 1–2) (n = 22, 39.3%)

Maculo-papular rash (Grade 1–2) (n = 8, 14.3%)

Infusion-related reactions (Grade 1–2) (n = 12, 21.4%)

Infections (Grade ≥ 3, n = 2; 3.6%)

Febrile neutropenia (Grade ≥ 3, n = 3; 5.3%)

Serious AEs: n = 14 (25%)

Lethal toxicity: n = 1 (1.8%) due to lung infection

The results of this phase II trial indicate that B-R as first-line treatment for splenic MZL is safe. According to the authors, B-R led to fast and durable disease control with a high response rate and with 13% of patients achieving CR after only three B-R cycles. The investigators are urging for further randomized prospective trials comparing B-R to R treatment for the ultimate validation of these results.

Dec 8, 2016

Dec 6, 2016

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The European Lymphoma Institute is comprised of a network of top European specialists in the field of lymphoma who are dedicated to research, training and education. Together they look to define strategies to analyse and characterize lymphoma and its common diagnostic procedures and therapeutic standards, as well as to facilitate clinical and fundamental research. This all results in the advancement of lymphoma research and it guarantees equal access for all patients to the best possible care.